Proteins and peptides

Last updated: April 27, 2022

Summarytoggle arrow icon

Proteins are large biomolecules consisting of more than 50 amino acids connected by multiple peptide bonds, while peptides are small biomolecules consisting of less than 50 amino acids. Proteins fulfill a variety of functions, including regulating physiological activity and providing structure to cells, and their functions are closely tied to their conformation. After ingestion, dietary proteins are denatured by gastric acid and subsequently cleaved by pepsin and proteases into monopeptides, dipeptides, tripeptides, and tetrapeptides. These end products are absorbed in the small intestine via proton symporter and Na+-coupled carrier proteins. Intracellularly, endogenous proteins are degraded by the ubiquitin proteasome system, while endocytosed dietary proteins are degraded by the lysosome. Accumulation of damaged or misfolded proteins/peptides has been observed in many neurological diseases such as Alzheimer disease, Parkinson disease, Huntington disease, Creutzfeldt-Jakob disease, and myotonic muscular dystrophy.

Protein structuretoggle arrow icon


Digestion and absorption of dietary proteinstoggle arrow icon

Important proteases of the gastrointestinal tract
Proteases Location Reaction Product
Endopeptidases: split peptide bonds within the polypeptide chain



  • Oligopeptides
  • Oligopeptides

Pancreatic elastase
  • Oligopeptides
Exopeptidases: split peptide bonds from end AAs Carboxypeptidases: split unspecific end AAs from C-terminal Carboxypeptidase A
  • Activated from zymogen procarboxypeptidase A by trypsin
  • Cleaves bonds involving aromatic AAs
  • AAs
Carboxypeptidase B
  • Activated from zymogen procarboxypeptidase B by trypsin
  • Cleaves bonds involving basic AAs
  • AAs
  • Cleaves unspecific end AAs from N-terminal
  • AAs
  • Cleaves dipeptides
  • AAs

Trypsinogen is first activated by enteropeptidase via proteolytic cleavage at the N-terminal. The resulting trypsin then activates other zymogens, including further trypsinogen (positive feedback loop).

The inactive zymogen pepsinogen is activated to pepsin by gastric acid.


Protein degradation and associated diseasestoggle arrow icon

Protein degradation

Endogenous proteins (those synthesized in cells) are degraded by proteasomes. Exogenous proteins are degraded by lysosomes.

Ubiquitin proteasome system (UPS)

  • Description
    • Via ubiquitination, proteins are targeted for degradation in proteasomes.
    • Proteasome: a barrel-like protein complex consisting of two units that breaks down marked or damaged proteins into peptides via ATP hydrolysis of peptide bonds
    • Not all ubiquitinated proteins are marked for degradation. In fact, ubiquitination may communicate changes to protein activity, location, or interactions.
    • Either a single ubiquitin molecule (monoubiquitylation) or a chain of ubiquitin (polyubiquitylation) can be added to the protein.
  • Pathway
    1. Ubiquitination: addition of ubiquitin to the ε-amino group of lysine residues of a substrate protein; occurs in three stages
      • Activation: performed by ubiquitin-activating enzymes (E1s)
      • Conjugation: performed by ubiquitin-conjugating enzymes (E2s)
      • Ligation: performed by ubiquitin ligases (E3s)
    2. Degradation

Some cases of Parkinson disease have been linked to defects in the ubiquitin-proteasome system.


Examples of diseases associated with aberrant proteolysis

There are many diseases associated with aberrant proteolysis; this list is not exhaustive.


Referencestoggle arrow icon

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  7. Cooper GM. The Cell: A Molecular Approach. Sinauer Associates ; 2000
  8. Rapley R, Whitehouse D. Molecular Biology and Biotechnology. Royal Society of Chemistry ; 2015
  9. Kaplan. USMLE Step 1 Lecture Notes 2016: Physiology. Kaplan Publishing ; 2015

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 Evidence-based content, created and peer-reviewed by physicians. Read the disclaimer